DESCRIPTION: The goal of this proposal is to substantiate certain reported effects of weak, 60 Hz electromagnetic fields on cell functions, and to define a cellular mechanism for the effects. The proposed work begins with an attempt to reproduce c-myc proto-oncogenes in CEM-CM3 T-lymphoblastoid cells. A magnetic field exposure system with identical sham set-up will be built to duplicate the setting. After the further experiments employing 60 Hz electric fields of 2-200 Mv/m alone, (corresponding to about 3-300 mA/m(2) of current density in the culture medium), or in addition to magnetic field and its induced current, will be performed. To amplify the electromagnetic field effect on carcinogenesis, a two-stage carcinogenesis model system, i.e., the methylcholanthrene-initiated, retinoid suppressed C3H/10T(1/2) fibroblasts, will be used to test the hypothesis that electromagnetic field acts as a promoter rather than as an initiator. The timing and the extent of expression of the transformed phenotype, proto-oncogene expression, and proliferation of initiated cells will be determined.Electromagnetic field-induced calcium signals in these cells and in lymphoblastoid cells will be measured and related to protein kinase C activation and other downstream functions, to test the hypothesis that electromagnetic field-induced calcium influx is a primary or secondary messenger in transducing signals related to carcinogenic promotion. The origin and mechanism of inducing calcium signals by electromagnetic field will be investigated, by using channel blockers, calmodulin inhibitors, and calcium pump modulators, and by matching the response frequency windows with hypothetical resonance amplification by intra-, extra-, and trans-membrane circuits. The outcome is expected to explain, and to define the significance limits of biological effects of weak electromagnetic field corresponding to environmental exposures.